乳腺癌亚型中 CD47 和 Calreticulin 的表达以及抗 CD47 对巨噬细胞介导的吞噬作用的抑制作用

IF 1.6 4区 医学 Q4 ONCOLOGY Anticancer research Pub Date : 2024-11-01 DOI:10.21873/anticanres.17318
Juthamard Chantaraamporn, Phattarin Pothipan, Titipatima Sakulterdkiat, Burana Khiankaew, Lalita Lumkul, Photsathorn Mutapat, Phichamon Phetchahwang, Jisnuson Svasti, Voraratt Champattanachai
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引用次数: 0

摘要

背景/目的:巨噬细胞介导的癌症免疫逃避受 "分化簇 47(CD47)--一种抗吞噬细胞信号 "和 "钙网蛋白(CALR)--一种促吞噬细胞信号 "之间平衡的调节。CD47 在各种癌症中高度表达。然而,CD47和CALR在乳腺癌中的表达谱,尤其是在不同激素受体亚型中的表达谱,以及CD47阻断在巨噬细胞介导的治疗中的作用,目前还不十分清楚:采用免疫组化方法检测乳腺癌和邻近正常组织中 CD47 和 CALR 的表达水平。为了研究 CD47 阻断疗法的效果,测定了乳腺癌细胞系中 CD47 和 CALR 的表达。用单克隆 CD47 抗体(B6H12)治疗乳腺癌时,进行了体外巨噬细胞介导的吞噬作用:结果:CD47和CALR在乳腺癌组织中过表达,它们的上调与激素受体亚型有关。Luminal A型乳腺癌患者的CD47水平较高,而三阴性乳腺癌(TNBC)患者的CALR水平较高。在Luminal A(MCF-7)和TNBC(MDA-MB-231)亚型乳腺癌细胞系中,CD47和CALR的水平也有所升高。有趣的是,MCF-7 细胞表面 CD47/CALR 的表达比明显更高。此外,体外吞噬试验显示,阻断 CD47 可增强两种癌细胞中巨噬细胞介导的活性,MCF-7 中的吞噬程度明显更高:结论:本文提供了 CD47 和 CALR 在乳腺癌亚型中的表达谱以及基于 CD47 阻断的免疫疗法的益处。
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CD47 and Calreticulin Expression in Breast Cancer Subtypes and Anti-CD47 Inhibitory Effects in Macrophage-mediated Phagocytosis.

Background/aim: Macrophage-mediated cancer immune evasion is modulated by the balance between "the cluster of differentiation 47 (CD47), an anti-phagocytic signal" and "calreticulin (CALR), a pro-phagocytic signal". CD47 is highly expressed in various types of cancer. However, the expression profiles of CD47 and CALR in breast cancer, especially in different hormone receptor subtypes, and the effects of CD47 blockade in macrophage-mediated therapy are not well understood.

Materials and methods: The expression levels of CD47 and CALR were investigated in breast cancer and adjacent normal tissues using immunohistochemistry. To study the effects of CD47 blockade therapy, CD47 and CALR expression in breast cancer cell lines were determined. In vitro macrophage-mediated phagocytosis of breast cancer upon treatment with a monoclonal CD47 antibody (B6H12) were performed.

Results: CD47 and CALR were overexpressed in breast cancer tissues and their up-regulation was associated with hormone receptor subtypes. Patients with Luminal A breast cancer had higher levels of CD47, while patients with triple-negative breast cancer (TNBC) had higher levels of CALR. The levels of CD47 and CALR were also elevated in breast cancer cell lines of Luminal A (MCF-7) and TNBC (MDA-MB-231) subtypes. Interestingly, the expression ratio of surface CD47/CALR was significantly higher in MCF-7. Moreover, in vitro phagocytosis assays revealed that blockage of CD47 enhanced macrophage-mediated activity in both cancer cells with dramatically higher degrees of phagocytosis in MCF-7.

Conclusion: The expression profiles of CD47 and CALR in breast cancer subtypes and the benefit of CD47 blocking-based immunotherapy are herein provided.

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来源期刊
Anticancer research
Anticancer research 医学-肿瘤学
CiteScore
3.70
自引率
10.00%
发文量
566
审稿时长
2 months
期刊介绍: ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.
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